Unravelling the mechanisms causing murepavadin resistance in : lipopolysaccharide alterations and its consequences.

Introduction: Murepavadin is an antimicrobial peptide (AMP) in clinical development that selectively targets LptD and whose resistance profile remains unknown. We aimed to explore genomic modifications and consequences underlying murepavadin and/or colistin susceptibility.

Methods: To define genomic mechanisms underlying resistance, we performed two approaches: 1) a genome-wide association study (GWAS) in a clinical collection (n=496), considering >0.

A highly-safe live auxotrophic vaccine protecting against disease caused by non-typhoidal Salmonella Typhimurium in mice.

Background: Salmonella enterica serovar Typhimurium (S. Typhimurium) has become an important intestinal pathogen worldwide and is responsible for lethal invasive infections in populations at risk. There is at present an unmet need for preventive vaccines.

Comparison of the in vivo efficacy of ceftaroline fosamil, vancomycin and daptomycin in a murine model of methicillin-resistant Staphylococcus aureus bacteraemia.

The need for alternative drugs to treat methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia has led to a focus on ceftaroline, for which clinical data remain scarce. Herein, the efficacy of ceftaroline fosamil for the treatment of experimental MRSA bacteraemia was compared with that of approved therapies. Five MRSA strains were tested in an immunocompetent BALB/c bacteraemia model.

Double Auxotrophy to Improve the Safety of a Live Anti- Vaccine.

is an opportunistic nosocomial pathogen that causes serious infections in the respiratory tract of immunocompromised or critically ill patients, and it is also a significant source of bacteremia. Treatment of these infections can be complicated due to the emergence of multidrug-resistant strains worldwide. Hence, the development of prophylactic vaccines is a priority for at-risk patients.

A New Live Auxotrophic Vaccine Induces Cross-Protection against Infections in Mice.

The development of a whole-cell vaccine from bacteria auxotrophic for D-amino acids present in the bacterial cell wall is considered a promising strategy for providing protection against bacterial infections. Here, we constructed a prototype vaccine, consisting of a glutamate racemase-deficient mutant, for preventing infections. The deletion mutant lacks the gene and requires exogenous addition of D-glutamate for growth.

A live auxotrophic vaccine confers mucosal immunity and protection against lethal pneumonia caused by Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the leading causes of nosocomial pneumonia and its associated mortality. Moreover, extensively drug-resistant high-risk clones are globally widespread, presenting a major challenge to the healthcare systems. Despite this, no vaccine is available against this high-concerning pathogen.